All data collected and published to date indicate that fenofibrate is a safe and well-tolerated lipid-lowering drug. Since its introduction in 1975, fenofibrate has been evaluated in 131 short- and long-term non-U.S. clinical studies involving 8,836 patients. Additionally, data has been collected by a postmarketing surveillance program initiated in France in 1979. Two recently completed double-blind, placebo-controlled, randomized U.S. studies conducted in 374 patients with types IIa and IIb or types IV or V hyperlipoproteinemia provide further evidence of the safety of fenofibrate. In the U.S. studies, clinical adverse events occurred in 25% of fenofibrate-treated patients and 18% of placebo-treated patients. The 8% higher frequency of adverse effects with fenofibrate corresponds to the 6 to 11% frequency observed in European clinical trials. About 3% of patients receiving fenofibrate discontinued treatment because of clinical adverse reactions. The most common adverse reactions in all studies involved gastrointestinal, dermatologic, central nervous system or musculoskeletal systems. Laboratory abnormalities in the U.S. studies occurred in 16% of fenofibrate-treated patients and in 7% of placebo-treated patients resulting in a discontinuation of treatment in 2% and 1% of patients, respectively. The difference between the 2 U.S. groups (9%) is similar to the frequency observed in the short-term European studies (6%). The most frequently reported (3-7%) laboratory adverse reaction has been an increase in liver enzymes. These elevations were not associated with clinical or functional disturbances of hepatic function and they usually normalized with continued treatment. The safety profile of fenofibrate is superior to that of clofibrate and is at least equal to gemfibrozil. Fenofibrate is a safe drug for patients with hyperlipidemia based on the uniformity and consistency of its safety record in the European studies. U.S. studies, and European post-marketing surveillance.